This invention relates to the general field of regulation of the growth and repair of tubular, or luminal, structures.
Tubular structures within the body (including bronchi of the lung, the entire gastrointestinal tract from the esophagus to the anus, the ureters and urethra of the genitourinary system, the fallopian tubes and vas deferens of the reproductive system, and the blood vessels) are all subject to luminal constriction and obstruction to flow. As a result, tissues and organs downstream of the obstruction are deprived of vital elements and tissues and organs upstream are dammed up with toxic products.
Surgical repair is often indicated in an attempt to relieve these obstructions. However, the repair may be unsuccessful or short-lived due to accelerated obstruction and a recurrence of the events that led to the initial crisis. Overproliferation of smooth muscle cells (SMC) as part of the natural repair process may contribute to luminal occlusion. In the arterial system, for example, restenosis rates of 25 to 35% have been noted within three months following percutaneous balloon angioplasty, and current estimates of the life expectancy of saphenous venin bypass grafts do not exceed 7 years. In the gastrointestinal system, this same phenomenon presents as recurrent bowel obstruction after lysis of adhesions or surgical anastomotic repair, and in the reproductive system as an ineffective surgical repair of the fallopian tubes or vas deferens.
There have been various attempts to limit occlusion. For example, for blood vessels, effort has been directed at various circulating (intravenous) factors such as heparin. Such factors inhibit or stimulate the clotting process and may also affect smooth muscle cell proliferation. Attempt have also been made to control environmental factors such as blood pressure, cholesterol, or smoking (nicotine). As regards lungs, attempts to limit occlusion have been directed at aerosolized factors and modulators of vascular tone (e.g., bronchodialators) and control of mucous formation. Efforts concerning the genitourinary system have focused on maintaining adequate flow, e.g. by controlling pH to enhance the solubility of stone material or by mechanical means such as ultrasound energy to break-up stones or uretal stents.